DESCRIPTION: A focus of this proposal is to define the interdependence of pineal and ocular autoimmune responses. The hypothesis that experimental autoimmune pinealitis (EAP) affects pineal gland composition and activity will be tested by immunochemical and immunohistochemical assays of EAP affected pineal glands and by analysis of pineal neurohormone melatonin cycles in EAP affected rats. The hypothesis that organ specific events influence immunopathology in EAP and experimental autoimmune uveoretinitis (EAU) will be tested using immunomodulation, pineal gland transplantation, and immunohistochemistry. Specific experiments will include manipulation of the model to dissociated EAP and EAU and anterior chamber transplantation of pineal glands to characterized factors that lead to diversity of EAP and EAU. Additional experiments will evaluate pineal gland infiltrating lymphocytes for activation state and their effect on EAU upon transplantation to the anterior chamber. A complementary approach to define immunopathology of uveitis involves studying spontaneous occurring equine recurrent uveitis (ERU). There is strong evidence of ERU as a sequela to systemic infection with Leptospira interrogans. Similar postinfectious-immune etiologies have been proposed for human disease. Study of this more controlled, defined equine population will set directions of study in the more complex area of human uveitides. These experiments will employ strategies to locate bacteria or antigen directly in the eye, characterize ocular and pineal gland immune response, and define anti-ocular and anti-leptospiral responses with potential crossreactivity. This collaborative investigation involving clinical and laboratory efforts presents a unique opportunity to evaluate infectious-immune interaction in uveitis.